Biomedical subjects

F Cremer

Publications and source records attributed to F Cremer.

10 recordsLinked to original sources

PubMed2006

Chromosomal aberrations in 130 patients with multiple myeloma studied by interphase FISH: diagnostic and prognostic relevance.

The study described the molecular cytogenetic characterization of myeloma cells in 130 patients via interphase fluorescence in situ hybridization. Nine repetitive DNA probes (for chromosomes 3, 7, 9, 11, 15, 17, 18, X, and Y) as well as seven single-copy DNA probes (for chromosomes 13, 17, 21, and two each for chromosomes 5 and 22) were used for the hybridizations. Using this panel of probes, we were able to show aberrations in 86% of patients. Most of them had one to three aberrations. There was a distinct correlation between the number of aberrations per patient and the tumor stage. Thus, the proportion of patients with 8-12 aberrations increased from 16% in stage II to 26% in stage III. There were marked differences among the chromosomes with respect to the prevalence of genomic losses and gains and deletions of gene loci. Chromosomes 3, 5, 7, 9, 11, 15, and 21 showed a preference for genomic gains. Losses were most often found for chromosomes 13 and 17 (locus specific) as well as for the X and Y chromosomes. The frequency of monosomies and trisomies were approximately the same for chromosomes 15 and 18, which indicates a skewed pattern of distribution. We found two specific aberrations that caused distinct changes in the survival rates of the patients: deletion 13q14 (28% of patients) and translocation of the IGH locus 14q32 (79% of 39 patients who were analyzed separately). The results obtained in this study yielded data of extremely relevant prognostic value.

Adult↗

PubMed2005

Long-term survival after surgical intervention for bone disease in multiple myeloma.

BACKGROUND: We describe the surgical treatment, outcome and long-term survival of patients with multiple myeloma (MM) in response to conventional (CC) or high-dose (HDT) chemotherapy. PATIENTS AND METHODS: Eighty-four patients diagnosed with MM were recruited for the study (51 male, 33 female; median age 62 years) and consecutively surgically treated in a single institution during a 12-year period. The main end point of the study was overall survival after surgery. Cox regression analysis was used to estimate the effect of factors that may predict survival. RESULTS: Spinal surgery was performed in 54 cases, and 30 patients were surgically treated at the extremities. The post-surgical complication rate was low (17%; 14/84 patients). The median overall survival time was 47 months. Patients receiving HDT had a longer 5-year overall survival rate than patients receiving CC (51% versus 33%). Univariate predictors of mortality included age >65 years [risk ratio (RR) 1.62; P=0.023], osteolyses in long weight-bearing bones (RR 2.23; P=0.007) and an elevated C-reactive protein level >5 mg/l (RR 1.82; P=0.016); the latter remained significant as a predictor in multivariate analysis (RR 2.66; P=0.0209). CONCLUSIONS: Given the high number of patients reaching 5-year overall survival and the low post-surgery complication rate, surgery should pursue a long-term stable reconstruction of the affected bone.

Adult↗

PubMed2002

Comprehensive genetic counseling for families at risk for HNPCC: impact on distress and perceptions.

The aim of the study was to explore distress and health beliefs before and after comprehensive interdisciplinary counseling in families at risk for hereditary non-polyposis colorectal cancer (HNPCC). Results reported here were derived from a consecutive sample of 65 counselees [31 patients with colorectal cancer (CRC) and 34 unaffected at-risk persons] who participated in interdisciplinary counseling provided by human geneticists, surgeons, and psycho-oncologists before genetic testing. Data were collected from self-administered questionnaires before, as well as 4-6 weeks after, counseling. Distress and perceptions specific to HNPCC were assessed at both timepoints using standardized as well as author-derived instruments. Distress declined after counseling, as did worries related to HNPCC. An increase was found in personal belief in control of cancer risk, for instance, in the perceived efficacy of early detection of CRC. We also observed a trend toward greater anticipated ability to cope with a positive gene test after counseling. Changes after counseling were generally more pronounced for persons at risk, as compared to patients with cancer. The decrease in distress was partly attributable to an increase in personal self-confidence. One-third of the sample reported enhanced communication specific to hereditary disease within the family after counseling. A substantial minority, however, said they experienced increased worry and physical symptoms after counseling. Overall, counselees demonstrated less stress and perceived cancer threat as well as enhanced beliefs regarding personal control over cancer, suggesting an overall beneficial impact of comprehensive counseling. Further research is needed to identify those individuals most at risk for increased fear and worry related to HNPCC so that they may be most appropriately counseled.

Adult↗

PubMed2001

Bisphosphonates in multiple myeloma.

BACKGROUND: Multiple myeloma is a disease characterized by the neoplastic proliferation of a clone of plasma cells that can lead to bone destruction. Bisphosphonates are specific inhibitors of osteoclastic activity. Therefore, there is a pharmacological basis for their use in multiple myeloma. However, the exact clinical role of bisphosphonates in multiple myeloma remains unclear. OBJECTIVES: Primary: to determine whether adding bisphosphonates to standard therapy in multiple myeloma decreases skeletal-related morbidity (pathological fractures), skeletal-related mortality and overall mortality. Secondary: to determine the effects of bisphosphonates on pain, quality of life and incidence of hypercalcemia. SEARCH STRATEGY: We searched MEDLINE (1966 - June 2001), LILACS (1982 - June 2001), EMBASE (1974 - December 2000) and the Cochrane Controlled Trials Register (all years, latest Issue 03/2001) to identify all randomized trials in multiple myeloma. All of these references were accessed in order to identify trials related to the use of bisphosphonates in myeloma. All relevant references in each article were also scanned. We also performed a handsearch of relevant meeting proceedings from 1993 to 2000. Additionally, manufacturers of bisphosphonates and researchers in the field were contacted. SELECTION CRITERIA: Randomised trials with a parallel design on the use of bisphosphonate in myeloma compared with placebo or no treatment as a control group. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and abstracted data. A third reviewer checked all data after the extraction was completed. Statistical heterogeneity was tested using random and fixed effect models. All pooled data are reported using Peto odds ratios and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event. MAIN RESULTS: Eleven trials were included with 1113 patients analysed in bisphosphonates groups, and 1070 analysed in control groups. There was no significant statistical heterogeneity among trials for the endpoints selected for comparison in this review. The pooled analysis of the published evidence demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures [OR=0.59 (95% confidence interval (CI) 0.45-0.78); P=0.0001] and on amelioration of pain [OR = 0.59 (95%CI 0.46-0.76); P=0.00005]. However, the analysis of the effect of bisphosphonates on pain was based on clinically heterogeneous data and must be interpreted with caution. Although there was no statistical heterogeneity between groups, the benefit was most apparent with clodronate and pamidronate. In absolute terms, the result may be interpreted to mean that 10 (95%CI 7-20) patients with multiple myeloma should be treated to prevent one vertebral fracture, and 11 (95%CI 7-28) to prevent one patient experiencing pain. We found no significant effect of bisphosphonates on mortality, on the reduction of non-vertebral fractures or on the incidence of hypercalcemia. There were no significant adverse effects associated with the administration of bisphosphonates. Our results are based on the extraction of published data, which were sometimes poorly reported, and thus the results should be understood as the best possible summation of available evidence. REVIEWER'S CONCLUSIONS: Adding bisphosphonates to the treatment of myeloma reduces pathological vertebral fractures and pain but - from the published evidence - not mortality. On current evidence, clodronate or pamidronate may be the preferred agents.

Bone Diseases↗

PubMed2001

The delayed terminal flower phenotype is caused by a conditional mutation in the CENTRORADIALIS gene of snapdragon.

The snapdragon (Antirrhinum majus) centroradialis mutant (cen) is characterized by the development of a terminal flower, thereby replacing the normally open inflorescence by a closed inflorescence. In contrast to its Arabidopsis counterpart, terminal flower1, the cen-null mutant displays an almost constant number of lateral flowers below the terminal flower. Some partial revertants of an X-radiation-induced cen mutant showed a delayed formation of the terminal flower, resulting in a variable number of lateral flowers. The number of lateral flowers formed was shown to be environmentally controlled, with the fewer flowers formed under the stronger flower-inducing conditions. Plants displaying this "Delayed terminal flower" phenotype were found to be heterozygous for a mutant allele carrying a transposon in the coding region and an allele from which the transposon excised, leaving behind a 3-bp duplication as footprint. As a consequence, an iso-leucine is inserted between Asp148 and Gly149 in the CENTRORADIALIS protein. It is proposed that this mutation results in a low level of functional CEN activity, generating a phenotype that is more similar to the Arabidopsis Terminal flower phenotype.

Alleles↗

PubMed1995

Detection of minimal residual disease by polymerase chain reaction in B cell malignancies.

It was the aim of this study to examine the prognostic value of the detection of minimal residual disease (MRD), with the help of the polymerase chain reaction (PCR), in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) who underwent sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support, and in patients with acute myeloid leukemia (AML) of the subclass M4Eo who underwent high-dose consolidation therapy. Basis for the application of a PCR assay in these disease entities are the following specific gene rearrangements: the t(14;18) translocation in a high percentage of NHL, the clonal rearrangement of the Ig heavy chain locus resulting in a unique complementary determining region 3 (CDR3) for MM region and the inversion 16 characteristic for the M4Eo subclass of AML. Before the G-CSF-supported cytotoxic chemotherapy was given, 65% of the 52 patients with low- and intermediate-grade NHL enrolled into the study had PCR+ bone marrow (BM) and/or peripheral blood (PB) samples. The majority of patients (29 of 52) were autografted with a PCR+ transplant. The proportion of harvests containing t(14;18)+ cells was two-fold less in patients mobilized in first remission than in those with a history of previous treatment failure. This was also reflected when examining the B cell contents of the harvests measured as CD19+ cells with a 3.3-fold smaller proportion of CD19+ cells in leukapheresis (LP) products of patients mobilized in first remission. Patients who received a PCR- transplant are in remission and remained PCR- in BM and PB samples post-transplantation. Conversion to PCR-negativity in BM and PB samples post-transplantation was observed in 11 of 19 patients who were also in remission. In contrast, 6 of 29 patients who were autografted with PCR+ products relapsed, while 4 of them presented with PCR- samples on several occasions post-transplantation. In patients with MM, the assessment of MRD in PBPC harvests was based on the CDR3 regions of the Ig heavy chain locus as a marker for clonality. The great majority of LP products (17 out of 19) contained tumor cells. To prove positive enrichment procedures for the elimination of tumor cells, CD34+ and CD19+ cell fractions obtained from LP samples in an experimental setting via preparative flow cytometry were analyzed for MRD resulting in PCR-negativity for all CD34+ fractions. The results of the four patients with AML M4Eo and inversion 16 are preliminary, with a tendency of persistence of PCR-positivity after finishing the high-dose consolidation therapy. In one case, recurrence of disease was accompanied by an increase of the signal strength in the PCR assay. Longer follow-up periods are necessary to determine the prognostic value of these PCR findings in the different disease entities.

Acute Disease↗

PubMed1991

Changes in mRNA level rhythmicity in the leaves of Sinapis alba during a lengthening of the photoperiod which induces flowering.

A previous study has shown that mRNAs exhibit complex patterns of diurnal rhythms in their quantity in the leaves of Sinapis alba during an 8 h light/16 h dark short day (SD). In order to determine whether this situation is rapidly modified in plants subjected to an extended light treatment, we have used in vitro translation and two-dimensional polyacrylamide gel electrophoresis, together with a strict gel comparison procedure giving a P = 0.03 certitude level, to analyse the mRNA complement at different times during a 22 h light/2 h dark long day (LD). During this LD, complex changes affected about 10% of the mRNAs. Thirty-four different patterns were observed. Some diurnal rhythms present in SD are not modified by the lengthening of the light period, but most are affected. Moreover, we have shown that some mRNAs presenting a constant quantity under a SD regime show an increase or a decrease during the first hours of the photoperiod lengthening. In Sinapis, this LD also induces flowering. All the changes in mRNA quantity detected thus parallel the photoperiodic induction of flowering in the leaves and are quantitative; no mRNA was shown to appear or to disappear.

Electrophoresis, Gel, Two-Dimensional↗

PubMed1990

Diurnal Rhythmicity in the Pattern of mRNAs in the Leaves of Sinapis alba.

Previous studies have shown that certain specific leaf mRNAs exhibit a diurnal rhythmicity in their quantity in higher plants. To determine whether this situation is restricted to a few mRNAs, or affects a large number, we have used in vitro translation and two-dimensional polyacrylamide gel electrophoresis to analyze the mRNA complement in leaves of Sinapis alba at different times during an 8-hour/16-hour day/night cycle. A method for the visual analysis of two-dimensional polyacrylamide gel electrophoresis was also developed. This method selected, at each sampling time, spots that were significant. It then selected, between two sampling times, intensity changes that were significant at the 0.02 confidence level. During a day/night cycle, complex rhythmic changes affected about 10% of the mRNAs. Nineteen different rhythm patterns were found. These 19 patterns fell into four main classes: mRNAs that increase during the light period and decrease during the dark, mRNAs that increase and then decrease during the light period, mRNAs that decrease during the light period and increase during the dark period, and mRNAs that increase and then decrease during the dark period.

Journal Article↗

PubMed1985

Method for extraction of proteins from green plant tissues for two-dimensional polyacrylamide gel electrophoresis.

A method has been developed for the extraction of proteins from green plant tissues to be used in two-dimensional polyacrylamide gel electrophoresis. Three purification steps were necessary to overcome the problems due to streaking, charge heterogeneity, and other artifacts: After it was ground in liquid nitrogen, the powdered material was stirred in the presence of insoluble polyvinylpyrrolidone for binding phenols, and sodium ascorbate for binding quinones; proteins were precipitated with ammonium sulfate, and the sample was dialyzed. Hundreds of proteins could be detected after Coomassie blue staining using 200 micrograms of proteins from apical buds of Sinapis alba L.

Chemical Phenomena↗

PubMed1983

[Acute interhemispheric subdural hematomas].

Three cases of acute interhemispheric subdural hematomas, one of which bilateral, are reported. These are secondary to cranial traumatism and/or to treatment by anticoagulants and have stereotyped clinical signs. Following a lucid period, intracranial hypertension appears, then a sudden predominantly crural hemiparesis or even paraplegia. The aspects shown by computerized tomography are characteristic. The literature and our experience suggest that the best treatment is complete evacuation of the hematoma by craniotomy performed before alteration of consciousness.

Aged↗